Photochemistry of 1- and 2-Methyl-5-aminotetrazoles: Structural Effects on Reaction Pathways

Article abstract of DOI:10.1021/acs.joc.6b02023

The influence of the position of the methyl substituent in 1- and 2-methyl-substituted 5-aminotetrazoles on the photochemistry of these molecules is evaluated. The two compounds were isolated in an argon matrix (15 K) and the matrix was subjected to in situ narrowband UV excitation at different wavelengths, which induce selectively photochemical transformations of different species (reactants and initially formed photoproducts). The progress of the reactions was followed by infrared spectroscopy, supported by quantum chemical calculations. It is shown that the photochemistries of the two isomers, 1-methyl-(1H)-tetrazole-5-amine (1a) and 2-methyl-(2H)-tetrazole-5-amine (1b), although resulting in a common intermediate diazirine 3, which undergoes subsequent photoconversion into 1-amino-3-methylcarbodiimide (H₂N-N=C=N-CH₃), show marked differences: formation of the amino cyanamide 4 (H₂N-N(CH₃)-C=N) is only observed from the photocleavage of the isomer 1a, whereas formation of the nitrile imine 2 (H₂N-C^-=N⁺=N-CH₃) is only obtained from photolysis of 1b. The exclusive formation of nitrile imine from the isomer 1b points to the possibility that only the 2H-tetrazoles forms can give a direct access to nitrile imines, while observation of the amino cyanamide 4 represents a novel reaction pathway in the photochemistry of tetrazoles and seems to be characteristic of 1H-tetrazoles. The structural and vibrational characterization of both reactants and photoproducts has been undertaken.

Full text of DOI:10.1021/acs.joc.6b02023

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Article
Photochemistry of 1- and 2-methyl-5-aminotetrazoles:
structural effects on reaction pathways
Amin Ismael, Rui Fausto, and Maria Lurdes Santos Cristiano
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b02023 • Publication Date (Web): 03 Nov 2016
Downloaded from http://pubs.acs.org on November 4, 2016
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Photochemistry of 1- and 2-methyl-5-aminotetrazoles:
structural effects on reaction pathways
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A. Ismael,†,‡ R. Fausto‡,* and M. L. S. Cristiano†,*
† CCMAR and Department of Chemistry and Pharmacy, F.C.T., University of Algarve, Pꢀ8005ꢀ039 Faro (Portugal)
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‡CQC, Department of Chemistry, University of Coimbra, Pꢀ3004ꢀ535 Coimbra (Portugal)
Eꢀmail: mcristi@ualg.pt; rfausto@ci.uc.pt
Keywords: Tetrazoles, Matrix isolation, Photocleavage mechanisms, Structureꢀreactivity relationships, Nitrile
imines, Diazirines, Carbodiimides, FTIR Spectroscopy
Abstract
The influence of the position of the methyl substituent in 1ꢀ and 2ꢀmethylꢀsubstituted 5ꢀ
aminotetrazoles on the photochemistry of these molecules is evaluated. The two compounds
were isolated in an argon matrix (15 K) and the matrix was subjected to in situ narrowband UV
excitation at different wavelengths, which induce selectively photochemical transformations of
different species (reactants and initiallyꢀformed photoproducts). The progress of the reactions
was followed by infrared spectroscopy, supported by quantum chemical calculations. It is
shown that the photochemistries of the two isomers, 1ꢀmethylꢀ(1H)ꢀtetrazoleꢀ5ꢀamine (1a) and
2ꢀmethylꢀ(2H)ꢀtetrazoleꢀ5ꢀamine (1b), although resulting in a common intermediate diazirine 3,
which undergoes subsequent photoconversion into 1ꢀaminoꢀ3ꢀmethylcarbodiimide (H2N–
N=C=N–CH3), show marked differences: formation of the amino cyanamide 4 (H2N–N(CH3)–
C≡N) is only observed from the photocleavage of the isomer 1a, whereas formation of the
nitrile imine 2 (H2N–C–=N+=N–CH3) is only obtained from photolysis of 1b. The exclusive
formation of nitrile imine from the isomer 1b points to the possibility that only the 2Hꢀtetrazoles
forms can give a direct access to nitrile imines, while observation of the amino cyanamide 4
represents a novel reaction pathway in the photochemistry of tetrazoles and seems to be
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characteristic of 1Hꢀtetrazoles. The structural and vibrational characterization of both reactants
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and photoproducts has been undertaken.
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Introduction
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After many decades of intense research on the structure, chemical properties, reactivity
and applications of tetrazoles, the scientific interest in the tetrazole chemotype remains
perennial. In the last few years another major application of tetrazoles came to light, with the
tetrazoleꢀbased photoclick chemistry providing a powerful tool for proteome profiling in living
cells.1–3 To this aim, several 2,5ꢀdisubstituted tetrazoles served as starting materials for in situ
generation of nitrile imine dipolar species, through UVꢀinduced photocleavage of the tetrazole,
via extrusion of N2. The nitrile imine dipolar species then react with an alkene dipolarophile,
through a 1,3ꢀdipolar cycloaddition reaction.4–10 Of course, these and other applications of
tetrazoles involving lightꢀinduced processes rely on their photochemistry, with a deeper
understanding enabling the design of better systems.
The photochemistry of tetrazole itself was studied for the first time by Maier et al.11
Primary and secondary processes were observed, leading to different photoproducts, such as
nitrile imine, carbodiimide, cyanamide and hydrogen cyanide. During the last decade, the
photoreactivity of a range of tetrazole derivatives has been widely investigated, in solution and
in the rigid environment of solid matrices, resulting in a wealth of information that unraveled
the potential of tetrazoles as precursors of a wide variety of new scaffolds, through
photolysis.12,13
More recently, several studies on the photolysis of tetrazoles under lowꢀtemperature
matrixꢀisolation conditions were focused on the efficient generation, capture and
characterization of unstable nitrile imines.14–19 It was postulated from these studies that
substituents play a major role on the structural characteristics of nitrile imines, this being
particularly noticeable by the νCNN antiꢀsymmetric stretching infrared (IR) absorption of the
nitrile imine moiety, which appears over a wide range of frequencies (2000ꢀ2250 cm–1).15,19 It
was proposed that nitrile imines with IR absorptions above 2200 cm−1 have essentially
propargylic character, possessing a CN triple bond, while those with IR absorptions below ca.
2200 cm−1 are more likely to be of allenic character. Additionally, all nitrile imines were
reported to isomerize to the corresponding carbodiimides, both thermally and photochemically.
However, most studies directed to the use of tetrazoles as photoprecursors of reactive
intermediates and unusual molecules are based on 2,5ꢀdisubstituted tetrazoles,11,14–19 Even in 5ꢀ
substituted tetrazoles, where the tetrazole ring bears a labile hydrogen as substituent, it was
observed that the 2Hꢀtautomer was the predominant form isolated in the matrix,14,17,19 in keeping
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with the behavior observed for the parent tetrazole.20 Thus, the matrix photochemistry of 1,5ꢀ
disubstituted tetrazoles remains mostly unexplored, apart from the work by Begué et al.19 on the
photolysis of 1ꢀmethylꢀ5ꢀphenyltetrazole, where the formation of carbodiimide as the final
photoproduct was demonstrated but no intermediates were detected. Although it could be
expected that only the 2,5ꢀdisubstituted tetrazoles would give direct access to nitrile imines, we
think that an investigation of the intermediates generated during photolysis of 1,5ꢀdisubstituted
tetrazoles may add relevant information regarding the reactivity of the tetrazole chemotype and
may also lead to new scaffolds.
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Herein we report, for the first time, the intermediates generated from photolysis of a
1,5ꢀdisubstituted tetrazole in solid argon.
To better understand the effects of the ring substitution pattern on the
photofragmentation pathways and species formed from diꢀsubstituted tetrazoles, the photolysis
of the isomeric 1ꢀmethylꢀ5ꢀaminotetrazoles and 2ꢀmethylꢀ5ꢀaminotetrazole was investigated,
using similar experimental conditions.
Earlier photochemical studies of 2ꢀmethylꢀ5ꢀaminotetrazole in solid argon16,21 revealed
the involvement of three different primary photochemical pathways: (1) tautomerization to
mesoionic 3ꢀmethylꢀ1Hꢀtetrazolꢀ3ꢀiumꢀ5ꢀaminide; (2) nitrogen elimination, with production of
3ꢀaminoꢀ1ꢀmethylnitrilimine, which isomerize into 1ꢀmethylꢀ1Hꢀdiazireneꢀ3ꢀamine; (3) ring
cleavage leading to methyl azide and cyanamide. Additionally, reactions of the primary
photoproducts were observed, leading to methylenimine and hydrogen isocyanide.16,21 Recent
studies on the photochemistry of a small library of tetrazoles,11,14–19 have demonstrated
formation of nitrile imines and these intermediates were found to isomerize, forming
carbodiimides as final products. However, in previous attempts to elucidate the photochemistry
of 2ꢀmethylꢀ5ꢀaminotetrazole, this isomerization was not observed. The coexistence of several
possible routes, resulting in various photoproducts (some may result from more than one route),
can easily lead to erroneous assignment of the IR absorptions.
We now discuss results of our investigation on the photochemistry of 1ꢀmethylꢀ5ꢀ
aminotetrazole and 2ꢀmethylꢀ5ꢀaminotetrazole using narrowband tunable UVꢀlaser irradiation.
This approach allows to induce the photoreactions of the isolated species selectively, providing
data for further clarification of the photochemistry of these compounds. A comparison of the
photochemistry of both isomers provides more information regarding the effects of the ring
substitution pattern on the photofragmentation pathways of diꢀsubstituted tetrazoles.. It is worth
noting that 5ꢀaminotetrazoles are important building blocks for the preparation of nitrogenꢀ
bridged saccharylꢀtetrazole conjugates, a group of ligands that have demonstrated to act as
selective copper chelators, affording copper complexes with cytotoxic properties.22
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Results and Discussion
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Photochemistry of matrix-isolated 1-methyl-5-aminotetrazole
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As described in the Experimental Section, a sample of crystalline 1ꢀmethylꢀ5ꢀ
aminotetrazole, 1a, was sublimated under reduced pressure (at ≈60°C), and the vapors of the
compound were coꢀdeposited with argon (ca. 1:1000 molar ratio) onto a CsI substrate kept at
15 K. Figure 1a shows the infrared spectrum of 1a isolated in solid argon in the 3600ꢀ2900 and
2500ꢀ800 cm–1 regions. The full midꢀIR range spectrum of 1a and the corresponding B3LYP/6ꢀ
311++G(d,p) calculated spectrum are provided as Supporting Information, Figure S1.
In order to investigate the photochemistry of 1a, the deposited matrix was irradiated
with UV light, as described in Experimental Section. The sample was monitored after each
irradiation by recording its infrared spectrum.
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0.25
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Ar matrix (a)
0.10
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λ
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= 222 nm, 6 min. (
b)
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B3LYP/6ꢀ311++G(d,p) (d)
∅
∗
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∗
∗
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3500 3000
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Wavenumber / cmꢀ1
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Figure 1. (a) Experimental IR spectrum of 1ꢀmethylꢀ5ꢀaminotetrazole 1a, isolated in solid
argon. (b and c) Difference IR spectra, showing spectral changes upon irradiation: (b) after 6
min. of irradiation at λ = 222 nm (~17 mW) of matrix 1a; (c) after 100 min. of irradiation at λ =
325 nm (~22 mW), subsequent to the irradiation at λ = 222 nm for 6 min. In (c), the negative
bands, blue circles and green rhombi correspond to the consumed diazirine 3 and cyanamide 4,
respectively. The bands with red stars correspond to carbodiimide 5. (d) Theoretically calculated
IR spectra of diazirine 3, cyanamide 4, carbodiimide 5 and CNH 9.
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Compound 1a was irradiated with monochromatic UVꢀlight at λ = 222nm. Figure 1b
shows the matrix spectrum of 1a after irradiation for a total of 6 min., when around 60% of 1a
was consumed and photoproducts 3–9 were produced (see also Scheme 1). Photoproducts 3
(1822 cm−1) and 4 (2159 cm−1) appeared immediately after the first seconds of irradiation,
followed by the increase of bands due to photoproduct 5 (2113/2107 cm−1). Kinetic studies for
the photolysis of 1a (see Figure 2) indicated that the maximum amount of species 3 and 4 was
reached after 60 s of irradiation at λ = 222 nm, and then started decreasing gradually, while
bands due to photoproduct 5 kept increasing and those due two new photoproducts appeared.
These new compounds were easily identified as cyanamide 6 (2261 cm−1) and hydrogen
isocyanide 9 (2031 cm−1), based on previously reported IR spectra of these species in argon
matrix.14,23–26 Upon extended photolysis, new characteristic bands evolved, due to the
isomerization of cyanamide 6 into carbodiimide 8 (2169 cm−1), as previously reported.23
carbodiimide 5
cyanamide 6
diazirine 3
amino cyanamide 4
carbodiimide 8
CNH 9
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0.3
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360
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Figure 2. Kinetic profiles showing changes of populations of the photoproducts 3 (1822 cmꢀ1),
4 (2159 cmꢀ1), 5 (2113/2107cmꢀ1), 6 (2261 cmꢀ1), 8 (2169 cmꢀ1) and 9 (2031 cmꢀ1) upon
irradiation at λ = 222 nm of 1a. In these profiles, the “amount of photoproducts” corresponds to
the experimental integrated band intensities, with maxima at indicated frequencies. See the
Experimental Section for details.
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Proposed assignments for the infrared absorptions of 1a and 1b, and observed
photoproducts 2-9, are included as Supporting Information, Tables S1ꢀS10.
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Me
8
9
N
N
b
ꢀN2
h
NH2
e
h
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H2N
Me
N
4
H2N
C
N N Me
N
d
N
N
5
ꢀN2
1a
H2N
a
Me
N
N
3
H2N
N
HN C NH
c
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+
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CNH
HN CH2
H2N
9
N
h
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C N N Me
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H2N
N
N
2
Me
1b
Scheme 1. The photochemistry of matrixꢀisolated 1a and 1b was induced by using
monochromatic UV light, (a) black plain arrows indicate the proposed pathways for the
photolysis of tetrazoles 1a and 1b, at λ = 222 nm and λ = 250 nm, respectively, (b) violet dashed
arrows indicate the proposed pathways when the matrix was irradiated at λ = 325 nm.
Continuous irradiation of 1a at λ = 222 nm activates two primary photochemical pathways a
and b, then three different secondary pathways c, d and e. However, upon subsequent irradiation
of the same matrix at λ = 325 nm, only pathways e and d, were observed. Continuous irradiation
of 1b at λ = 250 nm generates photoproduct 2, which isomerises into 3, then decomposes
through two different photochemical pathways, c and d. However, upon subsequent irradiation
of the same matrix at λ = 325 nm, only isomerization of 2 into 3, and pathways d, were
observed.
The photoproducts 3 and 5 were readily identified as diazirine 3 and carbodiimide 5. As
will be disclosed in the next section, the same bands were observed from photolysis of isomer
1b in solid argon. The identification of products 3 and 5 was supported by theoretical
calculations and by data from previous photochemical studies of matrixꢀisolated tetrazoles.14,15,17
On the other hand, the immediate increase of distinctive absorption bands at 2159 cm−1 and
1688 cm−1 indicated the formation of an unknown primary photoproduct, 4, obtained
concomitantly with diazirine 3. These results suggest that the formation of photoproducts 3 and
4, occurring in the first stage of irradiation, involves two different pathways (a and b,
respectively), both resulting from photocleavage of the tetrazole 1a. Then, as secondary
processes, three different pathways are observed: pathways d and e correspond, respectively, to
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the rearrangement of primary photoproducts 3 and 4 to carbodiimide 5; pathway c involves the
decomposition of diazirine 3 into cyanamide 6 (that undergoes subsequent isomerization into
carbodiimide 8, at λ = 222 nm) and hydrogen isocyanide 9.
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It is noteworthy that the elusive diazirine 3 is one of the few observations of
antiaromatic 1Hꢀdiazirines. The capture of such antiaromatic (i.e., 4π systems) structures can be
quite challenging, and has only been observed in a few cases, either upon isolation in cryogenic
matrices of noble gases, 14,15,17,21,27,28 or in NMR monitored studies, at ꢀ50ºC.29
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To gather further evidence regarding the photocleavage pathways involved, a new
experiment was designed: after irradiation of tetrazole 1a (at λ = 222 nm, 60 s), and generation
of both photoproducts 3 and 4 in a maximal amount, we irradiated the matrix at λ = 325 nm,
where the tetrazole 1a was observed to be photostable but its photoproducts could be
transformed. These irradiation conditions resulted in photoreactions of the primary
photoproducts 3 and 4, leading to formation of carbodiimide 5, in large amount, as sole
photoproduct (see Figure 3, for kinetic profile). After 100 min. of irradiation at λ = 325 nm,
when all 3 and 4 were consumed, the bands corresponding to carbodiimide 5 remained
unaltered, even at extended irradiation times, indicating that this compound is photostable under
the conditions used.
100
75
diazirine 3
amino cyanamide 4
carbodiimide 5
50
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0
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80
100
Time / min.
Figure 3. Kinetic profiles showing consumption of matrixꢀisolated diazirine 3 (1822 cmꢀ1) and
amino cyanamide 4 (2159 cmꢀ1) and formation of carbodiimide 5 (2113/2107 cmꢀ1), upon
irradiation at λ = 325 nm. See the Experimental Section for details.
Altogether, the experimental evidence shows that irradiation at λ = 222 nm activates
three different secondary photochemical processes of decomposition of the primary
photoproducts 3 and 4: pathways c, d and e. However, when a matrix containing the
photoproducts 3 and 4 is irradiated at λ = 325 nm the photochemical pathway c is excluded,
leading to a much cleaner spectrum (without the bands from photoproducts 6-9). Figure 1c
shows the difference IR spectrum after irradiation at λ = 325 nm for 100 min., where we can
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observe the transformations of the primary photoproducts due to secondary photoreactions. The
negative bands correspond to the consumed photoproducts 3 and 4 while the positive bands
result from formation of photoproduct 5. Thus, when irradiating at λ = 325 nm we can
selectively activate pathways d and e, which involve photoisomerization of photoproducts 3 and
4 into carbodiimide 5. The spectrum in Figure 1c also shows the formation of some CNH 9,
which will be explained below.
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The unknown species 4 could be unambiguously identified as amino cyanamide from
comparison between experimental and calculated IR spectra. The absorption bands expected for
4 above 800 cm−1 are clearly observed in Figure 1c (as green rhombi) and assigned in Table 1.
The most characteristic band, at 2159 cm−1, is assigned to the νC≡N stretching mode, calculated
at 2233 cm−1. Also, a characteristic absorption at 1688 cm−1 fits the estimated vibration at 1627
cm−1, which corresponds to the δNH2 scissoring mode. The bands in the 1500ꢀ1400 cm−1 region
correlate well with the calculated bands, and are assigned to the three δCH3 bending modes. The
band calculated at 1038 cm−1 could not be ascribed with certainty, though it seems to
correspond mainly to one of the CH3 rocking modes, appearing overlapped with the mixed
νNN/wNH2 vibration of carbodiimide 5, observed in the experimental spectrum at 1042 cmꢀ1.
As can be seen in Figure 1c, in the experimental difference IR spectrum resulting from the
photochemistry of both 3 and 4 upon irradiation at λ = 325 nm, such superposition results in
nearly cancelation of both bands (from the consumed reagent 4 and the formed product 5). The
experimental absorption bands above 2900 cmꢀ1 were assigned to the antiꢀsymmetric νNH2
(3431 cm−1) and νCH3 (3054, 3008, and 2918 cm−1) stretching vibrations, although some of the
assignments shall be considered as tentative. Indeed, the bands due to the CH3 stretching modes
appearing in this spectral range are expected to have very low intensity, and the overlap of
absorptions from both photoproducts (4 and 5) is also expectable, since they have similar
predicted νNH2 and νCH3 stretching frequencies (see Tables S5 and S6 in Supporting
Information). All other bands of photoproduct 4, observed at 1333 (νN7C6), 1185 (νN7C1;
wNH2), 1133 (γCH3’) and 868 (wNH2) cm−1, nicely fit with the calculated data (see Table 1).
Table 1. Proposed band assignments for the observed IR bands of photoproduct amino
cyanamide 4 (argon matrix; 15 K), and B3LYP/6ꢀ311++G(d,p) calculated vibrational
wavenumbers (ν, cmꢀ1) and IR intensities (I, km molꢀ1) for this molecule.ª,b
Ar matrix
Calculated
Approximate description
c
I
I
ν
ν
3431
ꢀ
3054
3008
11
ꢀ
22
22
3445
3346
3044
3004
9.2
1.9
7.2
νNH2 as
νNH2 s
νCH3 as’’
νCH3 as’
16.3
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2918
2159
1688
1463
1434
1403
ꢀ
1333
1185
1133
1042
868
17
67
45
39
22
11
ꢀ
50
17
17
45
62
2919
2233
1627
1461
1437
1404
1281
1254
1197
1107
1038
875
48.2
161.6
25.6
8.5
14.5
2.5
6.2
18.1
3.2
νCH3 s
νC≡N
δNH2
δCH3 as’’
δCH3 as’
δCH3 s
γNH2
νN7C6
νN7C1 ; wNH2
γCH3’
γCH3’’
wNH2
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2.2
49.7
80.5
b
ª Calculated wavenumbers were scaled by 0.968. ν, stretching; δ, bending; γ, rocking; w,
wagging; s. symmetric; as, antiꢀsymmetric. The primes in the approximate description of the
methyl group vibrations refer to local symmetry of the mode, under assumption of methyl local
Cs symmetry. Experimental intensities, after 60 s of irradiation at λ = 222 nm, were obtained
from the measured absorbances, by normalization to the total intensity of the observed
counterparts.
c
Concerning pathway c, it should be noted that the formation of cyanamide 6 could in
principle result from either the cleavage of the tetrazole 1a, generating cyanamide and methyl
azide, or from cleavage of the diazirine 3, generating cyanamide 6 and methylenimine 7.
However its formation via cleavage of the tetrazole 1a can be ruled out, since no evidence of
methyl azide in the photolyzed matrix could be found. According to the available spectroscopic
data, the νNNN antiꢀsymmetric mode of methyl azide gives rise to an intense absorption band
around 2100 cm−1.30 This expected intense band could not be observed, although we need to
consider that it could be overlapped by the intense band due to carbodiimide 5, at 2113/2107
cm−1. Besides, several new bands could in principle also be assigned to the methyl azide.
However after irradiations at λ = 325 nm, where the 1a does not react and no formation of
methyl azide should be observed, these same bands kept increasing, providing clear indications
that they belong to other photoproducts, and excluding the presence of methyl azide as putative
photoproduct in the photolyzed matrix. This observation indicates that the formation of
cyanamide 6 arises exclusively from photolysis of diazirine 3, which can suffer a ringꢀopening
photoreaction leading to cyanamide 6 and methylenimine 7. It is wellꢀknown that the
photodecomposition of matrix isolated methylenimine 7 gives rise to hydrogen isocyanide 9 by
1,1ꢀH2 elimination.25,26 Also, evidence for the presence of these species (cyanamide 6,
methylenimine 7 and hydrogen isocyanide 9) was observed only after formation of diazirine 3.
We could assign some of the observed bands to methyl imine 7, although the assignment of
bands due to this species is tentative due to the low intrinsic intensities of the bands of this
species (see Table S8). However, formation of the photoproduct 9 was observed beyond doubt
and, according to the available knowledge regarding the photochemistry of 7, one can then
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expect that the formation of 9 should result essentially from the presence of methylenimine 7 in
the matrix.
As previously explained, formation of cyanamide 6 was not observed upon irradiation at
λ = 325 nm, suggesting that, at this wavelength, pathway c can be ruled out. However, as can be
observed in Figure 1c, irradiation at λ = 325 nm led to formation of a small amount of hydrogen
isocyanide 9. We propose that this compound results from photodecomposition of the remaining
methylenimine 7, obtained in the first stage of irradiation, at λ = 222 nm.
6
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The identification of the photoproducts was supported by results of earlier
investigations regarding the photochemistry of the parent 5ꢀamino tetrazole14 and of 2ꢀmethylꢀ5ꢀ
aminoꢀtetrazole 1b16,21, under lowꢀtemperature matrixꢀisolation conditions. In fact, a comparison
between the observed bands in the photolysis of tetrazole 1a and the ones reported from earlier
studies for the photolysis of the isomer 1b, reveals excellent correlation among several
absorption bands, a clear evidence that the same photoproducts, 3 and 6-9, were obtained in
both cases. However, the previous studies on 2,5ꢀsubstituited tetrazole 1b failed in the
correlation of one expected species, the carbodiimide 5. In the previously investigations on the
photolysis of 1b, several absorption bands were assigned to a methyl azide (including the
distinguishable bands at 2113/2017 cm−1) and different photodegradation pathways were
proposed, but the carbodiimide 5 was excluded as final photoproduct.
In view of these inconsistencies, we decided to reinvestigate the photolysis of 1b using
narrow band UV irradiation, which, as demonstrated above for 1a, can be expected also in this
case to allow inducing selective photoconversion of the initially formed photoproducts of 1b
without consuming this latter species. This procedure can help clarifying details of the
photochemistry of the compound.
Photochemistry of matrix-isolated 2-methyl-5-aminotetrazole
Figure 4b shows the IR spectra of the matrixꢀisolated 1b after irradiation at λ = 250 nm
(~40 mW) for total of 4 s, when around 50% of 1b was consumed, and bands corresponding to
six different species were detected: protoproducts 2, 3, 5-7 and 9. These photoproducts were
readily identified as nitrile imine 2, diazirine 3, carbodiimide 5, cyanamide 6, methylenimine 7
and hydrogen isocyanide 9, based on the previously described results for the photolysis of 1a
and on data reported from earlier studies on the photolysis of 1b.16,21 Indeed, in view of the
generation of diazirine 3 as intermediate from the photolysis of both isomers 1a and 1b, it is
reasonable to expect the same channels of photofragmentation of diazirene 3, with formation of
photoproducts 5-9 (pathways c and d) upon photolysis of both isomers. There is, however, one
relevant difference: in the case of isomer 1b, the diazirene 3 results from photoisomerization of
nitrile imine 2, detected during our experiments. The formation of cyanamide 6 and
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methylenimine 7 could result from either the photofragmentation of diazirine 3, as previously
described for the photolysis of 1a, or directly form nitrile imine 2, as was observed for the
parent unsubstituted 5ꢀaminotetrazole.14 However, during photolysis of 1b the bands due to
cyanamide 6 were only observed after formation of diazirine 3, and kept increasing even after
total consumption of nitrile imine 2 (see the kinetic profiles in Figure 5), in keeping with the
results obtained from the photolysis of 1a, where we never observed any evidence of formation
of nitrile imine species. It should also be noted that the formation of carbodiimide 8 was only
observed in a separate experiment, when a matrix containing the photoproduct cyanamide 6 was
irradiated at λ < 230 nm.
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0.7
0.6
Ar matrix (a)
0.2
0.1
0.0
0.06
▼
λ
= 250 nm, 4s (b)
▼
▼
▼
0.03
0.00
▼
•
•
▼
▼
∗
∗
∅
▼
▼
•
▼
∗
∗
▼
▼
∗
∅
∗
ꢀ0.03
ꢀ0.06
ꢀ0.2
0.050
0.025
0.000
ꢀ0.025
λ
= 325 nm, 4 min. (c)
∗
∗
∅
•
∗
∗
•
•
∗
∅
•
•
∗
∗
▼
▼
▼
▼
▼
▼
▼
▼
♦
▼
▼
▼
ꢀ0.050
0.04
λ
= 325 nm, 60 min. (
d
)
0.03
0.01
∗
∅
∗
∗
∗
∅
∗
∗
▼
∗
▼
•
•
•
▼
▼
•
•
ꢀ0.01
3500 3000
2000
1600
1200
800
400
Wavenumber / cmꢀ1
Figure 4. (a) Experimental IR spectrum of 2ꢀmethylꢀ5ꢀaminotetrazole 1b, in solid argon at 15
K. (b, c and d) Difference IR spectra in solid argon showing spectral changes: (b) after 4 s of
UV irradiation at λ = 250 nm (~40 mW) of matrix isolated 1b; (c) after 4 min. of irradiation at λ
= 325 nm (~22 mW) subsequently to the irradiation of 4 s at λ = 250 nm. In (c) the negative
bands with olive triangles correspond to the consumed nitrile imine 2. The blue circles and red
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stars are assigned to diazirine 3 and carbodiimide 5, respectively; (d) after +60 min. of
irradiation at λ = 325 nm, subsequently to the 4 min. of irradiation under the same conditions.
6
7
8
0.18
cyanamide 6
CNH 9
nitrile imine 2
diazirine 3
carbodiimide 5
0.16
0.14
0.12
0.10
0.08
0.06
0.04
0.02
0.00
9
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60
0
1
2
3
4
Time / sec.
Figure 5. Kinetic profiles showing changes of populations of the photoproducts 2 (1963 cmꢀ1)
3 (1822 cmꢀ1), 5 (2113/2107cmꢀ1), 6 (2261 cmꢀ1) and 9 (2031 cmꢀ1), upon irradiation at λ = 250
nm of matrixꢀisolated 1b. In these profiles, the “amount of photoproducts” corresponds to the
experimental integrated band intensities, with maxima at indicated frequencies. See the
Experimental Section for details.
In summary the nitrile imine 2 (1963/1937 cm−1) is the main species generated in the
first second of irradiation, starting to be consumed after two seconds of irradiation with
concomitant increase of diazirine 3 (1822 cm−1), followed by photoproducts: cyanamide 6 (2261
cm−1) hydrogen isocyanide 9 (2031 cm−1) and carbodiimide 5 (2113/2107 cm−1). Irradiations of
this same solid matrix at λ = 325 nm, where 1b remains photostable, resulted in two different
observations (see the experimental IR in Figure 4 and the kinetic profiles in Figure 6): i) during
the first 4 min of irradiation all the nitrile imine 2 is consumed, with concomitant increase of
diazirine 3 and carbodiimide 5; ii) after the first 4 min of irradiation, the bands due to diazirine 3
starts to decrease, with concomitant growth of those due to carbodiimide 5, as sole
photoproduct, until all the diazirine 3 is consumed. As observed during photolysis of the isomer
1a, when the matrix containing the photoproduct 3 (from isomer 1b) was irradiated at λ = 325
nm the photochemical pathway c was excluded.
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100
4
5
6
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75
50
25
0
nitrile imine 2
diazirine 3
carbodiimide 5
9
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60
0
10
20
30
40
50
60
Time / min.
Figure 6. Kinetic profiles showing changes of matrixꢀisolated nitrile imine 2 (1963 cmꢀ1) to
carbodiimide 5 (2113/2107 cmꢀ1) via diazirine 3 (1822 cmꢀ1) upon irradiation at λ = 325 nm. See
the Experimental Section for details.
These results unequivocally demonstrate that the 5ꢀamino tetrazole 1b follows the
photofragmentation patterns observed for other 2Hꢀtetrazoles, with generation of nitrile imine 2
by extrusion of N2, followed by its photoisomerization into diazirine 3 that also photoisomerizes
to carbodiimide 5 as final photoproduct.11,14–19 As previously reported, the experimental IR
bands at 1963 and 1937 cm−1 due to the νCNN antiꢀsymmetric stretching, suggests a significant
carbenic character of the amino nitrile imine 2.16 These results are in agreement with the ones
obtained for the parent Cꢀamino nitrile imine (which was ascribed to bear a contribution of
around 20% of the carbenic resonance hybrid).14
In contrast, during the photolysis of 1a we never observed any evidence of formation of
a nitrile imine species, even after carefully searching for evidence during the first few seconds
of irradiation (when usually the nitrile imine are known to be observed). This result may mean
that only 2Hꢀtetrazoles could provide direct access to nitrile imines. The formation of amino
cyanamide 4 from UVꢀirradiation of isomer 1a, observed for the first time from photolysis of
tetrazoles under low temperature matrices, is also a relevant result of the present investigation.
Conclusions
We isolated compounds 1a and 1b in solid argon and studied their matrix
photochemistry.
Photolysis of matrixꢀisolated 1a at λ = 222 nm results in species 3–9, obtained in two
stages. The photoproducts diazirine 3 and amino cyanamide 4 are obtained in a first stage of
irradiation (primary photoproducts), through two different pathways, both resulting from the
photocleavage of tetrazole 1a. In a second stage two different pathways are observed, involving
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isomerization of both diazirine 3 and amino cyanamide 4 into carbodiimide 5. Also a third
pathway is observed, involving decomposition of diazirine 3 into photoproducts 6-9. However,
with subsequent irradiations of the matrix containig compounds 3 and 4 at λ = 325 nm, we could
prevent decomposition of diazirine 3 and exclude this last photochemical pathway, simplifying
the interpretation of the experimental spectra and rendering the interpretation of the
photochemical pathways easier.
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Photolysis of matrixꢀisolated 1b at λ = 250 nm results in products, 2, 3, 5-7 and 9,
obtained in two stages. The nitrile imine 2 is the main species generated in the first second of
irradiation, isomerising readily into diazirine 3 (also obtained from photolysis of the matrixꢀ
isolated isomer 1a). These results unequivocally demonstrate that the amino tetrazole 1b
follows the same photofragmentation patterns observed for other 2Hꢀtetrazoles, with generation
of nitrile imine, by extrusion of N2, its photoisomerization into diazirine that subsequently
photoisomerises to give carbodiimide as final product.
Interestingly, we found that the photochemistry of the two isomers, 1a and 1b, although
resulting in the same intermediate diazirine 3, which undergo subsequent photoconversion into
carbodiimide 5, seems to follow different pathways. In fact, the amino cyanamide 4 was
exclusively obtained from photocleavage of the isomer 1a, whereas the nitrile imine 3 was
exclusively obtained during the photolysis of 1b. This exclusive formation of nitrile imine from
the isomer 1b could mean that only the 2Hꢀtetrazoles forms can give a direct access to nitrile
imines.
We could assign the vibrational absorptions of the various photoproducts and propose
the different photochemical pathways. However, the mechanistic pathway for formation of the
species 4 upon irradiation of isomer 1a is not clear. We postulate the formation of nitrene
species, which could have different structures, with only the one resulting from 1a enabling
formation of aminocyanamide 4. This could explain the different photochemical pathways
observed for isomers 1a and 2a. Further research is needed to clarify this last point.
Experimental Section
General Information. The chemicals used were of analytical grade and were used
without further purification. When required, solvents were freshly distilled from appropriate
drying agents before use. The solvents for extraction were of technical grade. Melting points
recorded are uncorrected. Mass spectra were obtained by electron ionization (EI) at 70 eV.
NMR (400 MHz) spectra were measured using TMS as the internal reference (δ = 0.0 ppm).
Preparation of compounds. Methyltetrazoleꢀ5ꢀamines (1a, 1b) were prepared through
methylation of commercially available 5ꢀaminotetrazole monohydrate, as previously
described.31
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1-Methyl-(1H)-tetrazole-5-amine (1a): colorless needles (6.1 g; 51% yield), m.p.
220ꢀ221 ºC (lit, 220 ºC31); 1H NMR (400 MHz, CDCl3): δ 4.15 (3H, s); MS (EI): m/z 99 [M]+.
2-Methyl-(2H)-tetrazole-5-amine (1b): colorless needles (3.0 g, 25% yield), m.p.
104ꢀ105 ºC (lit, 104 ºC31); 1H NMR (400 MHz, CDCl3): δ 3.32 (3H, s); MS (EI): m/z 99 [M]+.
Matrix Preparation, Infrared Spectroscopy. The matrix was prepared by
codeposition of the matrix gas (argon, 99.9998%, obtained from Air Liquid) and vapors of the
tetrazole under analysis (1a or 1b) produced by sublimation onto the cooled CsI substrate of the
cryostat in a specially designed variableꢀtemperature miniꢀoven assembled inside the cryostat.
The cryogenic system was based on a closedꢀcycle helium refrigeration system with a DEꢀ202A
expander. The temperature of the CsI substrate during deposition was 15 K. The infrared
spectrum of matrixꢀisolated compounds was obtained using a Fourier transform infrared
spectrometer equipped with a deuterated triglycinesulfate (DTGS) detector and a Ge/KBr beam
splitter with 0.5 cm−1 spectral resolution.
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UV-Laser Irradiation Experiments. The matrix was irradiated through the outer
quartz window of the cryostat using a narrow band (fwhm ~0.2 cmꢀ1) with the frequencyꢀ
doubled signal beam of a QuantaꢀRay MOPOꢀSL pulsed optical parametric oscillator, pumped
with a pulsed Nd:YAG laser (repetition rate = 10 Hz, pulse energy ≈1-5 mJ, duration = 10 ns).
The UV light used to induce the initial photochemistry of 1a and 1b was selected according to
the UVꢀvis spectra obtained in ethanol at room temperature, which show an absorption
maximum at ~222 nm and ~248 nm, respectively. (See Figure S2 in supporting information)
Theoretical Calculations. Quantumꢀchemical calculations were performed with density
functional theory using the valence tripleꢀζ polarized 6ꢀ311++G(d,p) basis set32,33 and the
B3LYP functional.34,35 The optimization of geometries was followed by harmonic vibrational
calculations undertaken at the same level of theory. The calculated harmonic vibrational
frequencies were scaled by a factor of 0.968 obtained by leastꢀsquares linear fit of the
experimental versus calculated frequencies of 4 (Figure S3, Supporting Information). The
calculated frequencies were then used, to simulate the spectra using Lorentzian functions with
fwhm equal to 4 cmꢀ1 and to assist the analysis of the experimental spectra. All of the
calculations were performed with the Gaussian 09 suite of programs.36
Kinetic Measurements. Figure 2 shows one experiment where the species isolated in
the matrix were irradiated for a total amount of 6 min., at λ = 222, when around 60% of 1a was
consumed and several different photoproducts (3-9) were formed. Figure 3 shows a different
experiment where the first irradiation was performed at λ = 222 nm, to generate the maximum
amount of diazirine 3 and amino cyanamide 4. During this experiment, generation of 5 and 6
were also observed. The outset of the kinetics in Figure 3 corresponds to the end (60 s) of the
previous irradiation (λ = 222 nm). For the second part of the experiments, with irradiation at λ =
325 nm, the relative amounts of 3, 4, and 5 were assumed as 100%, 100%, and 0%,
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respectively. After 100 min, 3 and 5 were completely consumed, and the produced amount of 5
was set to 100%. Figure 5 shows one experiment where the species isolated in the matrix were
irradiated for a total amount of 4 sec. at λ = 250, when around 50% of 1b was consumed and
several different photoproducts (2, 3, 5, 6 and 9) were formed. The aim of the experiment
performed with irradiation at λ = 250 nm was to produce the maximum amount of nitrile imine
2. Generation of species 3, 5 and 6 was also observed. The outset of the kinetics in Figure 6
corresponds to the end of the previous irradiation (λ = 250 nm). For the experiments carried out
with irradiation at λ = 325 nm, the relative amounts of 2, 3, and 5 were assumed as 100%, 0%,
and 0%, respectively. After 60 min of this irradiation, 2 and 3 were completely consumed, and
the generated amount of 5 was set to 100%. At 4 min, the total amount of 2 and 5 was 46.7%
and achieved the bottom. The residual was parameterized to 53% as the maximal amount of 3
generated. All the amounts of species shown in Figures 2, 3, 5 and 6 correspond to the
experimental integrated band intensities, with maxima at indicated frequencies.
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Associated Content
Supporting information
Leastꢀsquares linear fit of the experimental versus calculated frequencies of 4; figures
showing UVꢀvis and experimental and calculated IR spectra of 1ꢀmethylꢀ5ꢀaminotetrazole 1a
and 2ꢀmethylꢀ5ꢀaminotetrazole 1b; proposed band assignments for the infrared spectrum of 1a,
1b and relevant photoproducts 2-9; Cartesian coordinates and electronic energies for all
optimized structures at the B3LYP/6ꢀ311++G(d,p) level. This material is available free of
charge via the internet at http://pubs.acs.org.
Author Information
Corresponding Author
*Eꢀmail: mcristi@ualg.pt
*Eꢀmail: rfausto@ci.uc.pt
Notes
The authors declare no competing financial interest.
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Acknowledgements
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9
The authors gratefully acknowledge Fundação para a Ciência e a Tecnologia (FCT), and
FEDER/COMPETE 2020ꢀUE, through projects UID/Multi/ 04326/2013 (Centre of Marine
Sciences ꢀ CCMAR), UI0313/QUI/2013 (Coimbra Chemistry Centre ꢀ CQC), PTDC/MARꢀ
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BIO/4132/2014 and PTDC/QEQꢀQFI/3284/2014
– POCIꢀ01ꢀ0145ꢀFEDERꢀ016617. A. Ismael
thanks FCT for financial support through grant SFRH/BD/ 90435/2012.
References
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